scholarly journals Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway

1997 ◽  
Vol 2 (4) ◽  
pp. E10
Author(s):  
Uwe M. H. Schrell ◽  
Michael G. Rittig ◽  
Marc Anders ◽  
Franklin Kiesewetter ◽  
Rolf Marschalek ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Cultures ◽  
Strand Break ◽  
Term Treatment ◽  
Dna Strand Break ◽  
Meningioma Cell ◽  
Dna Strand

Meningiomas, which invade intracranial bone structures and the adjacent connective tissue, are frequently unresectable because of their aggressive and recalcitrant growth behavior. They have a high recurrence rate, and in approximately 10% of these tumors there is an increased risk of malignancy. Significant morbidity and mortality rates associated with recurrent meningiomas demand nonsurgical approaches. To date, adjuvant hormonal treatment has not proven beneficial. The anticancer drug hydroxyurea was therefore tested for its potential use in the treatment of meningiomas. Early-passaged cell cultures were established from 20 different meningiomas. The addition of 5 X 10−4 and 10−3 M hydroxyurea over a period of 5 to 9 days resulted in a remarkable decrease in cell proliferation and even blocked tumor cell growth when compared with untreated cells. A significant arrest of meningioma cell growth in the S phase of the cell cycle was revealed on DNA flow cytometry. Electron micrographs of hydroxyurea-treated tumor cells showed ultrastructural features consistent with apoptosis, and light microscopy demonstrated DNA fragmentation by in situ DNA strand break labeling. Short-term treatment of meningioma cell cultures with hydroxyurea for 24 to 48 hours resulted in discrete oligonucleosomal fragments (DNA ladder), another characteristic sign of apoptosis. In addition to the in vitro studies, tissue from five different meningiomas was transplanted into nude mice followed by treatment with 0.5 mg/g body weight hydroxyurea over 15 days. In situ DNA strand break labeling demonstrated DNA fragmentation in distinct regions with different tumor cell densities in all hydroxyurea-treated meningioma transplants. These data provide evidence that hydroxyurea is a powerful inhibitor of meningioma cell growth, most likely by causing apoptosis in the tumor cells. Thus, hydroxyurea may be a suitable chemotherapeutic agent for the long-term treatment of unresectable or semi- to malignant meningiomas, or for preventing recurrent growth of meningiomas after resection.

Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway

1997 ◽  
Vol 86 (5) ◽  
pp. 845-852 ◽  
Author(s):  
Uwe M. H. Schrell ◽  
Michael G. Rittig ◽  
Marc Anders ◽  
Franklin Kiesewetter ◽  
Rolf Marschalek ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Strand Break ◽  
Term Treatment ◽  
Content Type ◽  
Dna Strand Break ◽  
Meningioma Cell ◽  
Dna Strand ◽  
Fine Print

✓ Meningiomas, which invade intracranial bone structures and the adjacent connective tissue, are frequently unresectable because of their aggressive and recalcitrant growth behavior. They have a high recurrence rate, and in approximately 10% of these tumors there is an increased risk of malignancy. Significant morbidity and mortality rates associated with recurrent meningiomas demand nonsurgical approaches. To date, adjuvant hormonal treatment has not proven beneficial. The anticancer drug hydroxyurea was therefore tested for its potential use in the treatment of meningiomas. Early-passaged cell cultures were established from 20 different meningiomas. The addition of 5 × 10−4 and 10−3 M hydroxyurea over a period of 5 to 9 days resulted in a remarkable decrease in cell proliferation and even blocked tumor cell growth when compared with untreated cells. A significant arrest of meningioma cell growth in the S phase of the cell cycle was revealed on DNA flow cytometry. Electron micrographs of hydroxyurea-treated tumor cells showed ultrastructural features consistent with apoptosis, and light microscopy demonstrated DNA fragmentation by in situ DNA strand break labeling. Short-term treatment of meningioma cell cultures with hydroxyurea for 24 to 48 hours resulted in discrete oligonucleosomal fragments (DNA ladder), another characteristic sign of apoptosis. In addition to the in vitro studies, tissue from five different meningiomas was transplanted into nude mice followed by treatment with 0.5 mg/g body weight hydroxyurea over 15 days. In situ DNA strand break labeling demonstrated DNA fragmentation in distinct regions with different tumor cell densities in all hydroxyurea-treated meningioma transplants. These data provide evidence that hydroxyurea is a powerful inhibitor of meningioma cell growth, most likely by causing apoptosis in the tumor cells. Thus, hydroxyurea may be a suitable chemotherapeutic agent for the long-term treatment of unresectable or semi- to malignant meningiomas, or for preventing recurrent growth of meningiomas after resection.

Rotary Beveling for In Situ Thin-Section Microscopy of Cell Cultures

1981 ◽  
Vol 39 ◽  
pp. 550-551
Author(s):  
Dean A. Handley ◽  
Jack T. Alexander ◽  
Shu Chien
Keyword(s):  
Cell Growth ◽  
Cell Cultures ◽  
Molecular Interactions ◽  
Convenient Method ◽  
Petri Dish ◽  
Simple Method ◽  
Thin Section Microscopy ◽  
Thin Sectioning ◽  
Organic Fluids

In situ preparation of cell cultures for ultrastructural investigations is a convenient method by which fixation, dehydration and embedment are carried out in the culture petri dish. The in situ method offers the advantage of preserving the native orientation of cell-cell interactions, junctional regions and overlapping configurations. In order to section after embedment, the petri dish is usually separated from the polymerized resin by either differential cryo-contraction or solvation in organic fluids. The remaining resin block must be re-embedded before sectioning. Although removal of the petri dish may not disrupt the native cellular geometry, it does sacrifice what is now recognized as an important characteristic of cell growth: cell-substratum molecular interactions. To preserve the topographic cell-substratum relationship, we developed a simple method of tapered rotary beveling to reduce the petri dish thickness to a dimension suitable for direct thin sectioning.

The invariance of the total direct DNA strand break yield

2011 ◽  
Vol 38 (7) ◽  
pp. 4147-4153 ◽  
Author(s):  
M. A. Bernal ◽  
C. E. deAlmeida ◽  
C. Sampaio ◽  
S. Incerti ◽  
C. Champion ◽  
...  
Keyword(s):  
Strand Break ◽  
Dna Strand Break ◽  
Dna Strand ◽  
Break Yield

scholarly journals Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties

2020 ◽  
Author(s):  
Katja Maria Bendtsen ◽  
Louise Gren ◽  
Vilhelm Berg Malmborg ◽  
Pravesh Chandra Shukla ◽  
Martin Tunér ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Diesel Exhaust ◽  
Strand Break ◽  
Diesel Exhaust Particles ◽  
Ultra Low Sulfur Diesel ◽  
Dna Strand Break ◽  
Diesel Particles ◽  
Exhaust Particles ◽  
Dna Strand ◽  
Low Sulfur

Abstract Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O 2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O 2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28 and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m 2 /g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 mg/mg) and acid-extractable metal content (0.9-16 mg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in liver on day 90 correlated with acellular particle-induced ROS.Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights particle size, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.

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